2022 Fiscal Year Final Research Report
Development of Pancreatic Cancer Therapy via Cancer Softening Action by Stromal Inhibition
Project/Area Number |
19K09112
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Hirosaki University |
Principal Investigator |
Daisuke Kudo 弘前大学, 医学研究科, 客員研究員 (00587024)
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Co-Investigator(Kenkyū-buntansha) |
石戸 圭之輔 弘前大学, 医学研究科, 准教授 (00436023)
長瀬 勇人 弘前大学, 医学部附属病院, 助教 (10750862)
吉田 枝里 弘前大学, 医学部附属病院, 助教 (20648886)
袴田 健一 弘前大学, 医学研究科, 教授 (30271802)
木村 憲央 弘前大学, 医学研究科, 講師 (60436029)
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Project Period (FY) |
2019-04-01 – 2023-03-31
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Keywords | 膵星細胞 / 浸潤性膵管癌 |
Outline of Final Research Achievements |
Normally, isolated PSCs change from a round to spindle-shaped morphology to a star-shaped activated morphology after a few days in culture. However, when 0.5 mM MU was administered to the medium of PSCs isolated from 8-week-old B6 mice, the growth rate decreased and more cells retained their round morphology. Next, the isolated PSCs and BxPC3, a human pancreatic cancer cell line, were subcutaneously transplanted into BALBc-nu/nu mice. After 4 weeks of observation, tumor volume was significantly smaller in the MU group compared to the control group. HE and EVG staining of the excised tumors revealed a decrease in collagen-like components in the stroma in the MU group. Microarray analysis of RNA extracted from tumors revealed that marker genes of cancer associated fibroblasts were significantly decreased in the MU group. Gene Ontology analysis revealed enrichments of extracellular matrix and response to oxygen levels were significantly decreased in the MU group.
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Free Research Field |
膵癌
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Academic Significance and Societal Importance of the Research Achievements |
膵癌間質をターゲットとした治療法は膵癌の新規治療の開発になり得る。MUは膵星細胞の活性化、癌関連線維芽細胞への変化を抑制することが明らかとなった。MUを投与したマウスでは、細胞外マトリックスおよび低酸素の反応が減弱することにより腫瘍径が小さくなることが示唆された。膵癌細胞へのMUの効果に関しては報告があるが、膵星細胞へのMUの効果はこれまで報告されておらず、膵癌治療の新しい切り口になる可能性がある。
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